A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Tekijät: Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D
Julkaisuvuosi: 2018
Journal: Nature Communications
Tietokannassa oleva lehden nimi: Nature Communications
Artikkelin numero: 5337
Vuosikerta: 9
Sivujen määrä: 9
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-07785-8
Verkko-osoite: https://doi.org/10.1038/s41467-018-07785-8
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/37049444
Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090G, located near NFKB1, on astrocytes. We demonstrated that chromatin is accessible at the risk locus, a prerequisite for its impact on astroglial function. The risk variant was associated with increased NF-κB signaling and target gene expression, driving lymphocyte recruitment, in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates and lesion sizes. Thus, our study establishes a link between genetic risk for MS (rs7665090G) and dysfunctional astrocyte responses associated with increased CNS access for peripheral immune cells. MS may therefore result from variant-driven dysregulation of the peripheral immune system and of the CNS, where perturbed CNS cell function aids in establishing local autoimmune inflammation.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
